The goal of this project is to gain further knowledge of renal function using the model of rapid change that occurs with growth and development. We will quantify functions during normal development and alter the rate of development of specific functions by treating with substrates. We will use substrate stimulation to elucidate biochemical and biophysical factors associated with active transport of organic anions. Transport will be stimulated and proteins involved in this transport process will be identified. This will be accomplished using amino acid incorporation into proteins in slices and in isolated tubules. The effect of substrate stimulation on PAH excretion in intact animals will be determined. We will quantitate the disappearance of PAH from the plasma of animals and the effect of substrate stimulation on the development of PAH Tm in the dog. Substrate stimulation will be used to gain insight into the transport of other anions. A preliminary study on the effect of diuretics in the newborn will be attempted. In addition, studies on the distribution of renal blood flow in newborn dogs will be done using silastic materials. These experiments will extend our current knowledge, broaden the scope of our previous work and increase our level of sophistication by developing new approaches to these problems. Thus, this research will provide new and important information on the basic mechanisms of drug transport, renal function during development and the role of various stimuli to development. Closely related projects will describe how the developing kidney effects or is affected by several drugs and how these might interact.